The segmental trisomy mouse (Ts65Dn) is an animal model of human Down syndrome (trisomy 21). It is trisomic only for the segment of chromosome 16 that is homologous to human chromosome 21. The adult Ts65Dn mouse demonstrates abnormal learning on spatial tasks. We found that the isolated hippocampus from this mouse also demonstrates abnormal long-term potentiation (LTP) and long term depression (LTD), models for learning and memory. Expression of the NMDA receptor main subunit (NR1) and of the alpha-1C Ca2+ channel subunit proteins, estimated by Western blotting, was not abnormal, however. Additionally, using in vivo 1H magnetic resonance spectroscopy we demonstrated an increased level of myoinositol in brains of Ts65Dn compared with control mice, consistent with our prior demonstration of increased myoinositol in brains of Down syndrome subjects. Thus, abnormal phosphoinositide signaling may contribute to mental retardation in Down syndrome, and can be examined in an appropriate mouse model. Kainate receptor-mediated excitatory postsynaptic currents occur in the spinal cord and are involved in nociception. Novel non-NMDA antagonists that we developed as anti-pain medication were shown to interfere with the effect of kainate in the rat spinal cord. - Kainate, Long-term potentiation, Long-term depression, Hippocampus, Down syndrome, Trisomy 65Dn mouse